SMART Team
2013-2014
Saint Dominic School SMART Team
Jacob Austin, Grace Gundrum, Grace Hilbert, Claire Hildebrand, Brigid Hughes, Sophia Jaskolski, Michael Kahler,
William Klingsporn, Deidre Lagore, Katherine MacDonald, Tyler Mark, Jackson Minessale, Sean O'Brien,
Matthew Peterman, Sam Reinbold, Alex Rusnak, Lydia Scott, Rachel Storts, Mia Vuckovich,
Michael Weisse, Nicholas (Mac) Wilke, Cade Wormington
Teacher: Donna LaFlamme
Mentor: Matthew Karafin, M.D., Medical College of Wisconsin, BloodCenter of Wisconsin
The RhD Protein
PDB: 3HD6
Primary Citation: F. Gruswitz, S. Chaudhary, J.D. Ho, A. Schlessinger, B. Pezeshki, C. Ho, A. Sali, C.M Westoff, R.M. Stroud (2019). Function of human Rh based on structure of RhCG at 2.1 Angstroms. PNAS 107:9638-9643
Format: Alpha carbon backbone
RP: Zcorp with plaster
Abstract:
Hemolytic disease of the newborn (HDN) occurs during pregnancy when the blood of an RhD positive (RhD+) baby comes in contact with the blood of an RhD negative (RhD-) mother. The mother’s immune system identifies the RhD protein on the baby’s erythrocytes as foreign, and produces anti-D antibodies which cross the placenta causing destruction of the baby’s red cells. Resulting symptoms range from mild jaundice and anemia to perinatal death. The RhD protein belongs to an ancient family of ammonia channels and is found on RhD+ erythrocytes but is missing from RhD- red cells. The St. Dominic SMART (Students Modeling A Research Topic) Team modeled RhD using 3-D printing technology. The model highlights RhD’s twelve transmembrane helices and the sidechains of its nonfunctional ammonia channel. Extracellular loops 3, 4, and 6 carry clusters of D antigen epitopes while loops 1, 2, and 5 do not play a major role in RhD antigenicity due to their sequence identity with RhCE. The RHD gene arose from gene duplication of the RHCE gene and has 93.8% homology. Along with RhAG (Rh associated glycoprotein) both RhD and RhCE are part of the trimeric Rh complex on erythrocytes, essential to the cells structural integrity. HDN research led to the discovery of RhD and to the highly complex Rh blood group system whose major antigens are D, C/c, and E/e. Hemolytic disease of the newborn is now preventable by injecting RhD- mothers with anti-D immunoglobin to prevent them from developing active immunity to their babies RhD+ erythrocytes.
Model Description:
Chain A (RhD is composed of only one chain)
Amino Terminus: Residue 1 is colored royal blue.
These residues are located on the cytoplasmic side of the erythrocyte membrane.
Carboxyl Terminus: Residue 443 is coloredcrimson.
These residuces are located on the cytoplasmic side of the erythrocyte membrane.
Alpha Helices: All 12 transmembrane helices are highlighted inaquamarine.
Extracellular Loop 3: Residues 172-183are coloredplum.
These residues carry a cluster of D specific epitopes.
Extracellular Loop 4: 237-242 is highlighted deeppink.
This loop carries a cluster of D specific epitopes.
Extracellular Loop 6: 361-384 is highlighted mediumpurple.
This loop carries a cluster of D specific epitopes.
Missing residues 362-383 is the clear to simulate the missing residues of Loop 6.
Extracellular Loops 1, 2, and 5 are highlightedlightseagreen.
Do not play a major role in RhD antigenicity because of their sequence homology with the RhCE protein.
Loop 1: 34-53 is missing residues 35-52 which are replaced with a clear section
Loop 2: 111-120
Loop 5: 294-301
Ammonia Channel Sidechains of RhCG: Phe130, Phe235, His185, His344, Leu193, Ile334, leu328, Glu329
Carbon-yellow; oxygen-hotpink; nitrogen-lightskyblue
In the evolutionary remnant of the ammonia channel found in the RhD protein the critical His185 and His344 residues are replaced by tyrosine and phenylalanine, respectively.
One hbond in the small beta sheet is colored cyan.
Structural supports are colored white.
The SMART Team Program is supported by a grant from the National Institutes of Health Clinical and Translational Science Award (NIH-CTSA UL1RR031973).